The goal of this clinical research effort is to understand the processing of pain in normals and in patients with neuropathic and/or chronic pain conditions. High resolution positron emission tomography and radiotracer techniques were used to assess regional brain activity via blood flow changes throughout the entire brain of normal humans and neuropathic pain patients. This allows us to determine if abnormalities exist in the neuropathy patients and compare these observations to experimental pain in normals. Over the past 8 months we have completed 19 Oxygen-15 water blood flow PET studies on 13 normal subjects, 4 patients with unilateral chronic neuropathic pain, 1 with bilateral neuropathy and 1 with unilateral post-herpetic neuralgia (PHN) in the trigeminal distribution. In the thirteen normals we determined the pattern of regional activation due to acute pain induced by subcutaneous injection of capsaicin and pain due to allodynia that arises subsequent to capsaicin injection. A wide variety of limbic and somatosensory regions both cortical and subcortical were activated in the two conditions compared to either resting state or normal light brushing. These data indicate that specific additional circuits are recruited in the allodynia condition compared to acute pain. Preliminary analysis of the scans of the patients indicates a consistent alteration in thalamic activity. We observe, in 4 out of 4 patients with unilateral neuropathy, a decrease in thalamic activity on the side of the brain that receives input from the neuropathic limb (3 left lower limb patients and 1 right lower limb patient). The observation of a decrease suggests that the thalamus is an important site for neural modulation of pain in chronic conditions. Functional magnetic resonance imaging (fMRI) is a new technique for studying regional brain activity without radioactive tracers. In collaboration with the Laboratory of Cardiac Energetics, NHLBI, we have begun to apply this method to studying pain processes in cerebral cortex of normals. A spoiled gradient recalled echo flash sequence and a quadature volume coil have been developed to obtain serial functional images of transaxial brain slices during noxious thermal stimulation at high anatomical resolution. The fMRI sequence is supplemented by two anatomical images that provide (a) high resolution grey matter/white matter/CSF anatomy and (b) an angiogram for blood vessel localization. Blood flow changes related to pain have been reproducibly imaged in primary somatosensory cortex.